To elucidate the mechanism of immune signal transduction to the hypothalamic neuroendocrine cells, we have measured [Ca^2] _i and the membrane currents or membrane potentials in hypothalamic supraoptic nucleus (SON) neurons, and melanotrophs of the pituitary pars intermedia.The results of the study are following :1. Prostaglandin E_2 (PGE_2) excited more than 80% of SON neurons tested.2. PGF_<2alpha> and the selective FP agonist, fluprostenol, mimicked the effects of PGE_2, whereas DP,EP,IP,TP agonists had little effect. Moreover, the EP1 antagonist, SC-51322 and EP/FP antagonist, ONO-NT-012, did not block the effects of PGE_2, whereas the latter antagonist blocked the effects of fluprostenol.3. PGE_2 induced non-selective cation currents in isolated SON neurons, whereas interleukin-1beta (1L-1beta) had little effect.4. PGE_2 inhibited spontaneous inhibitory postsynaptic currents in SON slice preparations, while it did not affect spontaneous excitatory postsynaptic currents.5. PGE_2 induced [Ca_<2+>] _i rises in isolated SON neurons, whereas 1L-1beta did not have a direct effect.6. PGE_2 inhibited voltage-dependent Ba^<2+> currents in rat melanotrophs through pertussis toxin sensitive G-proteins.